This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HYPOTHESIS The combination of irinotecan, temozolomide and vincristine will be well tolerated and will have synergistic anti-tumor activity. SPECIFIC AIMS To estimate the maximum tolerated dose (MTD) and recommended Phase 2 dose of oral irinotecan when administered with fixed-dose temozolomide and vincristine to children with refractory solid tumors or brain tumors. To define the toxicities of the above drug combination when administered on this schedule, and to describe any differences in toxicities between patients with low vs. high-risk UGT1A1 genotypes. To characterize the pharmacokinetics of oral irinotecan in children with refractory cancer who are receiving temozolomide and vincrisine. SECONDARY AIMS To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study. To describe the relationship of UGT1A1, UGT1A7, UGT1A9, and BCRP genotypes to the pharmacokinetics and pharmacodynamics of irinotecan metabolites.